The N ⁶ -Methyladenosine mRNA Methylase METTL3 Controls Cardiac Homeostasis and Hypertrophy

Abstract

Our study identified METTL3-mediated methylation of mRNA on N⁶-adenosines as a dynamic modification that is enhanced in response to hypertrophic stimuli and is necessary for a normal hypertrophic response in cardiomyocytes. Enhanced m6A RNA methylation results in compensated cardiac hypertrophy, whereas diminished m6A drives eccentric cardiomyocyte remodeling and dysfunction, highlighting the critical importance of this novel stress-response mechanism in the heart for maintaining normal cardiac function.